Table 1. Memantine and Amantadine IC50, (Amantadine IC50)/(Memantine IC50) Ratio, Ω, and ΔΔG° for Wild Type and Mutant NMDA Receptorsa.
memantine IC50 (μM) | N | amantadine IC50 (μM) | N | IC50 ratio | Ω | ΔΔG° | |
---|---|---|---|---|---|---|---|
WT | 0.54 ± 0.03 | 18 | 41 ± 5.6 | 6 | 75 | ||
GluN1 mutants | |||||||
N616Q | 5.9 ± 0.5 | 6 | 490 ± 73 | 10 | 83 | 1.1 | –0.06 |
N616D | 14 ± 1.3 | 7 | 590 ± 21 | 5 | 41 | 0.55 | 0.35 |
V644N | 12 ± 3.2 | 7 | 150 ± 27 | 8 | 12 | 0.16 | 1.1 |
V644T | 0.26 ± 0.06 | 13 | 44 ± 15 | 13 | 170 | 2.2 | –0.48 |
V644L | 0.26 ± 0.09 | 15 | 26 ± 6.5 | 11 | 100 | 1.3 | –0.17 |
A645N | 240 ± 16 | 11 | 1000 ± 68 | 11 | 4.4 | 0.06 | 1.7 |
A645L | 4.8 ± 0.4 | 9 | 53 ± 4.4 | 9 | 11 | 0.15 | 1.1 |
A645V | 0.60 ± 0.06 | 9 | 21 ± 0.8 | 14 | 34 | 0.46 | 0.47 |
V656N | 2.4 ± 0.2 | 8 | 94 ± 14 | 7 | 40 | 0.53 | 0.38 |
GluN2B mutants | |||||||
N615D | 1.3 ± 0.3 | 7 | 300 ± 17 | 9 | 230 | 3.1 | –0.67 |
N616D | 1.0 ± 0.1 | 6 | 56 ± 5.3 | 10 | 55 | 0.74 | 0.18 |
A639N | 3.6 ± 0.4 | 10 | 140 ± 26 | 11 | 39 | 0.51 | 0.39 |
V640N | 0.29 ± 0.03 | 11 | 12 ± 2.6 | 8 | 42 | 0.55 | 0.35 |
L643N | 34 ± 2.7 | 10 | 750 ± 130 | 13 | 22 | 0.29 | 0.73 |
A644N | 90 ± 2.0 | 9 | 340 ± 29 | 10 | 3.7 | 0.05 | 1.8 |
A644L | 0.29 ± 0.07 | 12 | 3.6 ± 0.4 | 12 | 12 | 0.17 | 1.0 |
A644V | 0.41 ± 0.05 | 14 | 10. ± 0.7 | 11 | 25 | 0.33 | 0.66 |
N= number of cells. IC50 ratio = IC50(amantadine)/IC50(memantine). Ω = [(wild type memantine IC50)(mutant amantadine IC50)]/[wild type amantadine IC50)/(mutant memantine IC50)]. ΔΔG0 = RT ln(Ω), where R = 1.987 kcal·mol–1·K–1 and T = 298 K.